دورية أكاديمية
Human Superantibodies to 3CLpro Inhibit Replication of SARS-CoV-2 across Variants
| العنوان: | Human Superantibodies to 3CLpro Inhibit Replication of SARS-CoV-2 across Variants |
|---|---|
| المؤلفون: | Kittirat Glab-ampai, Kanasap Kaewchim, Thanatsaran Saenlom, Watayagorn Thepsawat, Kodchakorn Mahasongkram, Nitat Sookrung, Wanpen Chaicumpa, Monrat Chulanetra |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 12, p 6587 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | SARS-CoV-2, major protease (3CLpro), human single-chain antibody variable fragments (HuscFvs), cell-penetrating antibody, superantibody, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Broadly effective and safe anti-coronavirus agent is existentially needed. Major protease (3CLpro) is a highly conserved enzyme of betacoronaviruses. The enzyme plays pivotal role in the virus replication cycle. Thus, it is a good target of a broadly effective anti-Betacoronavirus agent. In this study, human single-chain antibodies (HuscFvs) of the SARS-CoV-2 3CLpro were generated using phage display technology. The 3CLpro-bound phages were used to infect Escherichia coli host for the production the 3CLpro-bound HuscFvs. Computerized simulation was used to guide the selection of the phage infected-E. coli clones that produced HuscFvs with the 3CLpro inhibitory potential. HuscFvs of three phage infected-E. coli clones were predicted to form contact interface with residues for 3CLpro catalytic activity, substrate binding, and homodimerization. These HuscFvs were linked to a cell-penetrating peptide to make them cell-penetrable, i.e., became superantibodies. The superantibodies blocked the 3CLpro activity in vitro, were not toxic to human cells, traversed across membrane of 3CLpro-expressing cells to co-localize with the intracellular 3CLpro and most of all, they inhibited replication of authentic SARS-CoV-2 Wuhan wild type and α, β, δ, and Omicron variants that were tested. The superantibodies should be investigated further towards clinical application as a safe and broadly effective anti-Betacoronavirus agent. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/23/12/6587Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms23126587 |
| الوصول الحر: | https://doaj.org/article/7da3bb4295e84fbca9c431993ca7f141Test |
| رقم الانضمام: | edsdoj.7da3bb4295e84fbca9c431993ca7f141 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
|---|---|
| DOI: | 10.3390/ijms23126587 |